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BACKGROUND: We had previously reported that the administration of Gastrografin through a nasogastric tube (NGT-G) followed by long tube (LT) strategy could be a novel standard treatment for adhesive small bowel obstruction (ASBO); however, the long-term outcomes after initial improvement remain unknown. This study aimed to analyze the long-term outcomes of first-line NGT-G. METHODS: Enrolled patients with ASBO were randomly assigned to receive LT or NGT-G between July 2016 and November 2018. Thereafter, the cumulative surgery rate, cumulative recurrence rate, and overall survival (OS) rate were analyzed. In addition, subset analysis was conducted to determine the cumulative recurrence rate according to colonic contrast with Gastrografin at 24 h. RESULTS: A total of 223 patients (LT group, n = 111; NGT-G group, n = 112) were analyzed over a median follow-up duration of 550 days. The cumulative 1-year surgery rates, cumulative 1-year recurrence rates, and 1-year OS rates in the LT and NGT-G groups were 18.8% and 18.1%, 30.0% and 31.7%, and 99.1% and 96.6%, respectively; no significant differences were observed between both groups. In the NGT-G group, a negative colonic contrast at 24 h demonstrated a higher tendency for future recurrence compared with a positive colonic contrast at 24 h (1-year recurrence rate: negative contrast, 46.9% vs positive contrast, 27.6%). CONCLUSIONS: Gastrografin through a nasogastric tube followed by LT can be a promising treatment strategy for ASBO, with long-term efficacies equivalent to initial LT placement.
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Diatrizoato de Meglumina , Obstrução Intestinal , Intubação Gastrointestinal , Meios de Contraste/administração & dosagem , Diatrizoato de Meglumina/administração & dosagem , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/terapia , Intestino Delgado , Aderências Teciduais/complicações , Resultado do TratamentoRESUMO
INTRODUCTION: Etelcalcetide binds to the extracellular domain of the calcium-sensing receptor (CaSR), while cinacalcet binds to the 7-transmembrane domain of the CaSR; however, it is unknown, whether etelcalcetide has similar effects to cinacalcet on parathyroid hormone (PTH) secretion. MATERIALS AND METHODS: The PTH-calcium setpoint and maximum and minimum PTH secretion were determined using an 'in vivo setpoint analyses.' The PTH-calcium setpoint was obtained in a mouse model of primary hyperparathyroidism (PC) and wild-type (WT) mice, with PC mice divided into two groups. The setpoint was obtained after 7 days of etelcalcetide (3.0 mg/kg BW/day) or vehicle administration via anosmotic pump. After 7 days of crossover administration, the setpoint was obtained again. Parathyroid glands were obtained after crossover administration, and CaSR expression was analyzed by immunohistochemistry. RESULTS: Etelcalcetide administration significantly decreased the setpoint from 9.03 ± 0.56 mg/dL to 6.80 ± 0.28 mg/dL, which was restored to 8.81 ± 0.38 mg/dL after vehicle administration. In the second group of mice, vehicle administration did not alter the setpoint (8.84 ± 0.69 mg/dL to 8.98 ± 0.63 mg/dL), but subsequent etelcalcetide administration significantly decreased it to 7.10 ± 0.72 mg/dL. There was no significant change in maximum and minimum PTH secretion. Expression levels of parathyroid CaSR were lower in PC mice than in WT mice; however, no significant differences were observed between the two mouse groups. CONCLUSION: Etelcalcetide decreased the PTH-calcium setpoint without changing maximum and minimum PTH secretion in PC mice, suggesting that like cinacalcet, etelcalcetide has calcimimetic potency.
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Cálcio/metabolismo , Hiperparatireoidismo Primário/tratamento farmacológico , Hormônio Paratireóideo/metabolismo , Peptídeos/uso terapêutico , Animais , Cálcio/sangue , Creatinina/sangue , Humanos , Hiperparatireoidismo Primário/sangue , Magnésio/sangue , Masculino , Camundongos Transgênicos , Glândulas Paratireoides/metabolismo , Glândulas Paratireoides/patologia , Hormônio Paratireóideo/sangue , Peptídeos/administração & dosagem , Peptídeos/farmacologia , Fosfatos/sangue , Receptores de Detecção de Cálcio/metabolismo , Fatores de TempoRESUMO
INTRODUCTION: Etelcalcetide (Parsabiv®, AMG 416/ONO-5163) is a novel allosteric modulator for the calcium-sensing receptor approved for hemodialysis patients with secondary hyperparathyroidism of uremia. Etelcalcetide reduced parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism of uremia in clinical studies. However, its direct effect on parathyroid hormone secretion in human parathyroid cells remains unknown. This study aimed to determine if etelcalcetide suppresses parathyroid hormone secretion by human parathyroid cells in vitro. MATERIALS AND METHODS: We prepared primary cell cultures from human parathyroid tissue and determined calcium-sensing receptor expression levels by immunohistochemistry. Pathyroid tumors were removed from fourteen patients with primary hyperparathyrodism. Parathyroid tissue was dispersed with collagenase, resuspended in culture medium, incubated for 2 h with etelcalcetide and Ca2+, and the medium was then collected. Final etelcalcetide concentrations in the medium were 0.005-50 µmol/L. Levels of human parathyroid hormone in the medium were determined by enzyme-linked immunosorbent assay. RESULTS: In eight of the fourteen parathyroid cell cultures, extracellular Ca2+ reduced parathyroid hormone levels. In four of the eight parathyroid cell cultures which responded extracellular Ca2+, etelcalcetide reduced hormone secretion with the 50% effective concentrations of 0.57, 20.8, 0.42, and 0.57 µmol/L. Expression levels of the calcium-sensing receptor were significantly lower in primary hyperparathyroidism patient-derived parathyroid tissues compared with controls. CONCLUSION: This is the first report that etelcalcetide directly reduced parathyroid hormone secretion from the primary cultured human parathyroid cells from patients with primary hyperparathyroidism. To verify this conclusion, further studies are needed using secondary hyperparathyroidism patient-derived parathyroid cells.
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Hiperparatireoidismo Primário/patologia , Glândulas Paratireoides/patologia , Hormônio Paratireóideo/metabolismo , Peptídeos/farmacologia , Animais , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/química , RatosRESUMO
PURPOSE: Endoscopic clipping closure after colorectal endoscopic submucosal dissection (ESD) did not reduce the incidence of post-ESD coagulation syndrome (PECS) in our recent randomized controlled trial (RCT); however, the definition of PECS is still controversial. The aim of this study is to establish optimal definition of PECS with additional analysis of RCT based on another definition. METHODS: In this multicenter, single-blind RCT, individuals were randomly assigned to colorectal ESD followed by endoscopic clipping closure or non-closure. In this post hoc analysis, the definition of PECS was modified as both localized abdominal pain on visual analogue scale and inflammatory response (fever or leukocytosis), from either localized abdominal pain or inflammatory response in the original study. All participants underwent a computed tomography after ESD, and PECS was classified into type I, conventional PECS without extra-luminal air, and type II, PECS with peri-luminal air. RESULTS: A total of 155 patients (84 in the non-closure group and 71 in the closure group) were analyzed. As a result of criteria modification, 21 type I PECS and four type II PECS cases in the original study, which included patients with clear pain and inflammatory response, were downgraded to no adverse event and simple peri-luminal air, respectively. The frequency of PECS showed no significant difference between non-closure and closure groups. CONCLUSION: Clipping closure after colorectal ESD does not reduce the incidence of PECS regardless of the diagnostic criteria. Either localized abdominal pain or inflammatory response might be optimal criteria of PECS (UMIN000027031). TRIAL REGISTRATION NUMBER: UMIN000027031 DATE OF REGISTRATION: April 18, 2017.
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Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Dor Abdominal/etiologia , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/efeitos adversos , Humanos , Instrumentos Cirúrgicos , Resultado do TratamentoRESUMO
Ultrasonography (US) and power Doppler US (PDUS) are used worldwide for diagnosing rheumatoid arthritis (RA). Superb microvascular imaging (SMI) is a good tool for evaluating inflammatory activity. Thermal imaging is a noncontact, noninvasive procedure using skin temperature measurement. We report a case wherein the thermal and ultrasound images of the hand are compared and evaluated for inflammatory activity in patients with RA. Case: US imaging of the left hand of a 75-year-old woman with RA revealed a hypoechoic lesion of the left wrist joint. PDUS and SMI evaluated blood flow according to the blood flow at Grade 2. The temperature of the hypoechoic lesion with high blood flow was higher than that of the same location on the opposite side. This study shows that combining thermal and blood flow images may be useful for detecting inflammatory activity levels in RA patients.
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AIM: Adolescence is a crucial stage of psychological development and is critically vulnerable to the onset of psychopathology. Our understanding of how the maturation of endocrine, epigenetics, and brain circuit may underlie psychological development in adolescence, however, has not been integrated. Here, we introduce our research project, the population-neuroscience study of the Tokyo TEEN Cohort (pn-TTC), a longitudinal study to explore the neurobiological substrates of development during adolescence. METHODS: Participants in the first wave of the pn-TTC (pn-TTC-1) study were recruited from those of the TTC study, a large-scale epidemiological survey in which 3171 parent-adolescent pairs were recruited from the general population. Participants underwent psychological, cognitive, sociological, and physical assessment. Moreover, adolescents and their parents underwent magnetic resonance imaging (MRI; structural MRI, resting-state functional MRI, and magnetic resonance spectroscopy), and adolescents provided saliva samples for hormone analysis and for DNA analysis including epigenetics. Furthermore, the second wave (pn-TTC-2) followed similar methods as in the first wave. RESULTS: A total of 301 parent-adolescent pairs participated in the pn-TTC-1 study. Moreover, 281 adolescents participated in the pn-TTC-2 study, 238 of whom were recruited from the pn-TTC-1 sample. The instruction for data request is available at: http://value.umin.jp/data-resource.html. CONCLUSION: The pn-TTC project is a large-scale and population-neuroscience-based survey with a plan of longitudinal biennial follow up. Through this approach we seek to elucidate adolescent developmental mechanisms according to biopsychosocial models. This current biomarker research project, using minimally biased samples recruited from the general population, has the potential to expand the new research field of population neuroscience.
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Comportamento do Adolescente/fisiologia , Desenvolvimento do Adolescente/fisiologia , Sintomas Comportamentais/fisiopatologia , Encéfalo/diagnóstico por imagem , Eletroencefalografia , Epigênese Genética/genética , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Adolescente , Comportamento do Adolescente/psicologia , Sintomas Comportamentais/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pais , Saliva , Tóquio/epidemiologiaRESUMO
An alternative synthetic route toward a key intermediate in the total synthesis of isoschizogamine is described. The Claisen-Johnson rearrangement stereoselectively constructed a quaternary carbon. Trifluoroperacetic acid mediated the Baeyer-Villiger oxidation to form a bicyclic lactone. The Mukaiyama-Matsuo protocol converted the lactone into an α,ß-unsaturated lactone, that was used as the substrate for the rhodium-mediated 1,4-addition of an arylboronic acid.
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Alcaloides Indólicos/síntese química , Ácidos Borônicos/química , Alcaloides Indólicos/química , Lactonas/síntese química , Lactonas/química , Estrutura Molecular , Ródio/químicaRESUMO
Alzheimer's disease (AD) is a common neurological disease that causes dementia in humans. Although the reports of associated pathological genes have been increasing, the molecular mechanism leading to the accumulation of amyloid-ß (Aß) in human brain is still not well understood. To identify novel genes that cause accumulation of Aß in AD patients, we conducted an integrative analysis by combining a human genetic association study and transcriptome analysis in mouse brain. First, we examined genome-wide gene expression levels in the hippocampus, comparing them to amyloid Aß level in mice with mixed genetic backgrounds. Next, based on a GWAS statistics obtained by a previous study with human AD subjects, we obtained gene-based statistics from the SNP-based statistics. We combined p values from the two types of analysis across orthologous gene pairs in human and mouse into one p value for each gene to evaluate AD susceptibility. As a result, we found five genes with significant p values in this integrated analysis among the 373 genes analyzed. We also examined the gene expression level of these five genes in the hippocampus of independent human AD cases and control subjects. Two genes, LBH and SHF, showed lower expression levels in AD cases than control subjects. This is consistent with the gene expression levels of both the genes in mouse which were negatively correlated with Aß accumulation. These results, obtained from the integrative approach, suggest that LBH and SHF are associated with the AD pathogenesis.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas Nucleares , Polimorfismo de Nucleotídeo Único , Transcriptoma , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Proteínas de Ciclo Celular , Modelos Animais de Doenças , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Transgênicos , Proteínas Nucleares/genética , Fatores de TranscriçãoRESUMO
The trabecular bone score (TBS) is a new surrogate for trabecular bone microarchitecture assessment, independent of bone mineral density (BMD), calculated from pixel gray-level variations in the lumbar spine (LS) dual-energy X-ray absorptiometry (DXA) image. Although Teriparatide (TPTD) increased LS-BMD as well as TBS in 2 years, the precise time-course of these parameters was not well known. The aim of this study was to determine the changes in LS-BMD and the TBS in osteoporotic patients treated with TPTD, followed by minodronate (MINO). Primary osteoporotic patients with a low LS-BMD (T-score < -2.5) and/or at least one vertebral fracture were treated with TPTD subcutaneously at 20 µg/day for 12-24 months, followed by MINO (orally at 50 mg/once monthly) for 12 months. LS-BMD and the TBS were measured at 0, 3, 6, 12, and 24 months after the initiation of TPTD treatment, and 12 months after the initiation of MINO. The increments of LS-BMD, significant at 6 months, increased until 12 months, whereas the increments of TBS, significant at 3 months (0.035 ± 0.011; p = 0.045 vs. the baseline), stabilized until 12 months. TPTD treatment, followed by 12 months of MINO, maintained both BMD and the TBS. Comparing the increments of the TBS to those of LS-BMD, our results indicate that TPTD treatment improved trabecular microarchitecture faster than mineralization. TPTD treatment, followed by MINO, can maintain both BMD and the TBS.
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Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Difosfonatos/administração & dosagem , Imidazóis/administração & dosagem , Osteoporose/tratamento farmacológico , Teriparatida/administração & dosagem , Absorciometria de Fóton , Idoso , Osso Esponjoso/diagnóstico por imagem , Osso Esponjoso/efeitos dos fármacos , Osso Esponjoso/patologia , Feminino , Humanos , Vértebras Lombares , Masculino , Fraturas por Osteoporose/tratamento farmacológicoRESUMO
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-ß (Aß). The genes that govern this process, however, have remained elusive. To this end, we combined distinct mouse strains with transcriptomics to directly identify disease-relevant genes. We show that AD model mice (APP-Tg) with DBA/2 genetic backgrounds have significantly lower levels of Aß accumulation compared with SJL and C57BL/6 mice. We then applied brain transcriptomics to reveal the genes in DBA/2 that suppress Aß accumulation. To avoid detecting secondarily affected genes by Aß, we used non-Tg mice in the absence of Aß pathology and selected candidate genes differently expressed in DBA/2 mice. Additional transcriptome analysis of APP-Tg mice with mixed genetic backgrounds revealed kinesin light chain-1 (Klc1) as an Aß modifier, indicating a role for intracellular trafficking in Aß accumulation. Aß levels correlated with the expression levels of Klc1 splice variant E and the genotype of Klc1 in these APP-Tg mice. In humans, the expression levels of KLC1 variant E in brain and lymphocyte were significantly higher in AD patients compared with unaffected individuals. Finally, functional analysis using neuroblastoma cells showed that overexpression or knockdown of KLC1 variant E increases or decreases the production of Aß, respectively. The identification of KLC1 variant E suggests that the dysfunction of intracellular trafficking is a causative factor of Aß pathology. This unique combination of distinct mouse strains and model mice with transcriptomics is expected to be useful for the study of genetic mechanisms of other complex diseases.
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Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Isoformas de Proteínas/metabolismo , Doença de Alzheimer/genética , Animais , Encéfalo/metabolismo , Cruzamentos Genéticos , Perfilação da Expressão Gênica , Humanos , Cinesinas , Camundongos , Proteínas Associadas aos Microtúbulos/genética , Isoformas de Proteínas/genética , Especificidade da EspécieRESUMO
Anti-inflammatory effects have been reported in Perilla frutescens leaf extract (PE), which is a plant of the genus belonging to the Lamiaceae family. We examined the effect of PE on dextran sulfate sodium (DSS)-induced colitis. Preliminarily, PE was safely administered for 7 wk without any adverse effects. In the preventive protocol, mice were fed 1.5% DSS solution dissolved in distilled water (control group) or 0.54% PE solution (PE group) ad libitum for 7 days. In the therapeutic protocol, distilled water or 0.54% PE solution was given for 10 days just after administration of 1.5% DSS for 5 days. PE intake significantly improved body weight loss. The serum cytokine profile demonstrated that TNF-α, IL-17A, and IL-10 were significantly lower in the PE group than in the control group. In the therapeutic protocol, mice in the PE group showed significantly higher body weight and lower histological colitis scores compared with mice in the control group on day 15. The serum cytokine profile demonstrated that TGF-ß was significantly higher in the PE group than in the control group. In distal colon mRNA expression, TNF-α, and IL-17A were significantly downregulated. In vitro analyses of biologically active ingredients, such as luteolin, apigenin, and rosmarinic acid, in PE were performed. Luteolin suppressed production of proinflammatory cytokines, such as TNF-α, IL-1ß, IL-6, and IL-17A. Apigenin also suppressed secretion of IL-17A and increased the anti-inflammatory cytokine IL-10. Rosmarinic acid increased the regulatory T cell population. We conclude that PE might be useful in treatment and prevention of DSS-induced colitis.
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Anti-Inflamatórios/farmacologia , Colite/prevenção & controle , Colo/efeitos dos fármacos , Citocinas/sangue , Sulfato de Dextrana , Fármacos Gastrointestinais/farmacologia , Mediadores da Inflamação/sangue , Perilla frutescens , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Peso Corporal/efeitos dos fármacos , Colite/sangue , Colite/induzido quimicamente , Colite/genética , Colite/imunologia , Colo/imunologia , Colo/metabolismo , Citocinas/genética , Modelos Animais de Doenças , Feminino , Fármacos Gastrointestinais/química , Camundongos Endogâmicos C57BL , Perilla frutescens/química , Fitoterapia , Extratos Vegetais/química , Plantas Medicinais , RNA Mensageiro/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Células Th17/metabolismo , Fatores de TempoRESUMO
Chemotherapy improves the outcome of cancer treatment, but patients are sometimes forced to discontinue chemotherapy or drop out of a clinical trial due to adverse effects, such as gastrointestinal disturbances and suppression of bone marrow function. The objective of this study was to evaluate the safety and effectiveness of a mushroom product, active hexose correlated compound (AHCC), on chemotherapy-induced adverse effects and quality of life (QOL) in patients with cancer. Twenty-four patients with cancer received their first cycle of chemotherapy without AHCC and then received their second cycle with AHCC. During chemotherapy, we weekly evaluated adverse effects and QOL via a blood test, EORTC QLQ-C30 questionnaire, and DNA levels of herpes virus type 6 (HHV-6) in saliva. The DNA levels of HHV-6 were significantly increased after chemotherapy. Interestingly, administration of AHCC significantly decreased the levels of HHV-6 in saliva during chemotherapy and improved not only QOL scores in the EORTC QLQ-C30 questionnaire but also hematotoxicity and hepatotoxicity. These findings suggest that salivary HHV-6 levels may be a good biomarker of QOL in patients during chemotherapy, and that AHCC may have a beneficial effect on chemotherapy-associated adverse effects and QOL in patients with cancer undergoing chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores/análise , DNA Viral/análise , Herpesvirus Humano 6/genética , Neoplasias/tratamento farmacológico , Polissacarídeos/uso terapêutico , Saliva/virologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Qualidade de Vida , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Pregnancy and lactation-associated osteoporosis (PLO) is one of the rarest and most serious primary osteoporotic conditions that develops during the third trimester of gestation and/or early postpartum period. A history of PLO often causes individuals to hesitate when considering an additional child due to anxiety about recurrence risk. Reported here are details of a 29-year-old patient with PLO given aggressive treatment for osteoporosis with teriparatide who subsequently gave birth to a healthy child at age 33 without PLO recurrence. Further case studies are needed to examine the efficacy and safety of PLO treatment and to provide beneficial results for those who wish to have another pregnancy.
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Lymphoproliferative disorders (LPDs) are serious complications that arise in patients with rheumatoid arthritis (RA) receiving immunosuppressive drugs (ISDs). Here, we reported a 73-year-old woman diagnosed with RA at 60 years of age and treated with methotrexate, bucillamine, prednisolone, and infliximab. She was referred to our hospital, Osaka Metropolitan University Hospital, with general malaise, pancytopenia, a right adrenal mass, and enlarged periaortic lymph nodes. Epstein-Barr virus was detected in serum. We suspected LPD development and performed a bone marrow biopsy, on which no malignant cells could be detected. Upon ISDs withdrawal, her symptoms and blood counts improved, and the right adrenal mass and enlarged lymph nodes regressed. The patient was followed up for clinical LPD. However, 7 months after the initial visit to our hospital, she developed fever and pancytopenia. A repeat bone marrow biopsy confirmed the diagnosis of Epstein-Barr virus-positive diffuse large B-cell lymphoma complicated by haemophagocytic syndrome. After pulse steroid therapy, the patient received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, which resulted in a complete response. In conclusion, when LPDs develop in patients with RA during ISD treatment, LPDs can progress and complicate haemophagocytic syndrome after partial remission following ISDs withdrawal. Therefore, we should carefully follow up RA patients with LPDs, and aim to achieve an early diagnosis of LPD and promptly initiate chemotherapy.
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Artrite Reumatoide , Imunossupressores , Humanos , Feminino , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Idoso , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/administração & dosagem , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/tratamento farmacológico , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/complicações , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Antirreumáticos/administração & dosagem , Resultado do Tratamento , Indução de Remissão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
A 51-year-old woman with fever was admitted to our hospital. A computed tomography (CT) scan showed thickened colonic walls. Colonoscopy revealed erosion in the ileum and colon. Adult-onset Still's disease (AOSD) was diagnosed due to a subsequent sore throat and skin rash. Following AOSD treatment, methylprednisolone pulse therapy, followed by prednisolone and cyclosporine, was initiated. Despite achieving a temporary improvement, relapse occurred with fever, abdominal pain, with worsening CT and endoscopic findings. The reappearance of a skin rash confirmed an exacerbation of AOSD. Tocilizumab treatment alleviated the symptoms and improved the endoscopic findings. Considering their correlation with the symptoms and endoscopic findings, the observed gastrointestinal lesions may be linked to AOSD.
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An ungrounded human, such as a substation worker, receives contact currents when touching a grounded object in electric fields. In this article, contact currents and internal electric fields induced in the human when exposed to non-uniform electric fields at 50 Hz are numerically calculated. This is done using a realistic human model standing at a distance of 0.1-0.5 m from the grounded conductive object. We found that the relationship between the external electric field strength and the contact current obtained by calculation is in good agreement with previous measurements. Calculated results show that the contact currents largely depend on the distance, and that the induced electric fields in the tissues are proportional to the contact current regardless of the non-uniformity of the external electric field. Therefore, it is concluded that the contact current, rather than the spatial average of the external electric field, is more suitable for evaluating electric field dosimetry of tissues. The maximum induced electric field appears in the spinal cord in the central nervous system tissues, with the induced electric field in the spinal cord approaching the basic restriction (100 mV/m) of the new 2010 International Commission on Non-Ionizing Radiation Protection guidelines for occupational exposure, if the contact current is 0.5 mA.
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Condutividade Elétrica , Fontes de Energia Elétrica , Modelos Anatômicos , Adulto , Humanos , Masculino , RadiometriaRESUMO
A novel class of potent NaV1.7 inhibitors has been discovered. The replacement of diaryl ether in compound I was investigated to enhance mouse NaV1.7 inhibitory activity, which resulted in the discovery of N-aryl indoles. The introduction of the 3-methyl group is crucial for high NaV1.7 in vitro potency. The adjustment of lipophilicity led to the discovery of 2e. Compound 2e (DS43260857) demonstrated high in vitro potencies against both human and mouse NaV1.7 with high selectivity over NaV1.1, NaV1.5, and hERG. In vivo evaluations revealed 2e demonstrating potent efficacy in PSL mice with excellent pharmacokinetics.
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A first asymmetric total synthesis of (-)-isoschizogamine has been accomplished. Our synthesis features the facile construction of the carbon framework of the natural product through a Wagner-Meerwein rearrangement, a tandem metathesis, a stereoselective rhodium-mediated 1,4-addition of an arylboronic acid, and a ring-closing metathesis via a hemiaminal ether.
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Alcaloides/síntese química , Apocynaceae/química , Produtos Biológicos/síntese química , Indóis/síntese química , Ácidos Borônicos/química , Ciclização , Alcaloides Indólicos , Ródio/química , EstereoisomerismoRESUMO
A 71-year-old man was receiving follow-up examination because of a retention cyst in the pancreatic body that extended to the dorsal extrahepatic area, but presented to the Emergency Department at our hospital with dyspnea and cough. Chest X-ray showed a large amount of left-sided pleural effusion and abdominal computed tomography (CT) showed reduction in size of the cystic lesion. Biochemical testing of the pleural effusion revealed high levels of pancreatic enzymes. We, therefore, diagnosed rupture of the pancreatic cystic lesion into the chest cavity. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated stenosis of the pancreatic duct and leakage of contrast medium at the cystic lesion. CT after ERCP revealed leakage of contrast medium from the cystic lesion through the dorsal extrahepatic area into the chest cavity. Endoscopic naso-pancreatic drainage was performed, but the cystic lesion and pleural effusion remained unimproved. Distal pancreatectomy was, therefore, performed. Microscopic examination revealed eosinophilic infiltration of the pancreatic parenchyma, leading to a diagnosis of eosinophilic pancreatitis (EP). Pancreatic retention cyst secondary to chronic pancreatitis associated with eosinophilic infiltration was considered to have ruptured into the chest cavity. EP is a rare etiology of pancreatitis and few cases have been reported. This case was thus considered valuable.
Assuntos
Cisto Pancreático , Pancreatite , Idoso , Colangiopancreatografia Retrógrada Endoscópica , Humanos , Masculino , Pâncreas , Cisto Pancreático/complicações , Ductos Pancreáticos/patologia , Pancreatite/complicações , Pancreatite/patologiaRESUMO
PURPOSE: The standard first-line treatment for human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer (AGC) is trastuzumab in combination with cisplatin and fluoropyrimidines. We evaluated the efficacy and safety of S-1 and oxaliplatin (100 mg/m2) (SOX100) combined with trastuzumab, a monoclonal antibody against HER2 for HER2-positive AGC. METHODS: In this single-arm, multicenter phase II study, patients with HER2-positive AGC received S-1 (80-120 mg per day) orally on days 1-14, oxaliplatin (100 mg/m2) intravenously on day 1, and trastuzumab (8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks) intravenously. The primary end point was 1-year survival rate. The secondary end points included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety. RESULTS: A total of 25 patients from six centers were enrolled from December 2015 to March 2020. In the 25 patients evaluable for analysis, the 1-year survival rate was 70.8% [90% confidence interval (CI) = 55.5-86.1%], whereas the median OS, PFS, and ORR were 17.8 (95% CI 10.5-22.9) months, 7.6 (95% CI 5.0-10.9) months, and 75.0% (95% CI 53.3-90.2), respectively. Major grade 3/4 adverse events included anorexia (20%), anemia (16%), peripheral sensory neuropathy (16%), and diarrhea (15%). CONCLUSION: SOX100 combined with trastuzumab was effective with a favorable safety profile in patients with HER2-positive AGC.